In addition to their role in inactivating endotoxin, macrophages release many of the mediators associated with shock. These mediators include acid hydrolases, neutral proteases, oxygen free radicals, certain coagulation factors, and the following arachidonic acid derivatives: prostaglandins, thromboxanes, and leukotrienes. Macrophages also release certain monokines that modulate temperature regulation, intermediary metabolism, hormone secretion, and the immune system.
Interactions of Positive and Negative Feedback Mechanisms
Hemorrhage provokes a multitude of circulatory and metabolic derangements. Some of these changes are compensatory, and others are decompensatory. Some of these feedback mechanisms possess high gain and others possess low gain. Furthermore, the gain of any specific mechanism varies with the severity of the hemorrhage. For example, with only a slight loss of blood, Pa is maintained within the normal range and the gain of the baroreceptor reflexes is high. With greater losses of blood, when Pa is below 60 mm Hg (i.e., below the threshold for the baroreceptors), further reductions in pressure have no additional influence through the baroreceptor reflexes. Hence, below this critical pressure, the baroreceptor reflex gain is zero or near zero.
In general, with minor degrees of blood loss, the gains of negative feedback mechanisms are high, whereas those of positive feedback mechanisms are low. The opposite is true with more severe hemorrhage. The gains of the various mechanisms add algebraically. Therefore, whether a vicious cycle develops depends on whether the sum of the positive and negative gains exceeds 1. Total gains in excess of 1 are, of course, more likely to occur with severe losses of blood. Therefore, to avert a vicious cycle, serious hemorrhages must be treated quickly and intensively, preferably by whole blood transfusion, before the process becomes irreversible.
inversely with Qh. This relationship is represented by the vascular function curve, and it reflects the fact that as Qh increases, a greater fraction of the total blood volume resides in the arteries and a smaller volume resides in the veins.
2. The principal cardiac mechanisms that govern cardiac output are the changes in numbers of myocardial cross-bridges that interact and in the affinity of the contractile proteins for Ca++ . The principal factors that govern the vascular function curve are arterial and venous compliance, peripheral vascular resistance, and total blood volume.
3.
The equilibrium values of Qh and Pv that prevail under a given set of conditions are determined by the intersection of the cardiac and vascular function curves. At very low and very high heart rates, the heart is unable to produce adequate Qh. At very low heart rates, the increase in filling during diastole cannot compensate for the small number of cardiac contractions per minute. At very high heart rates, the large number of contractions per minute cannot compensate for the inadequate filling time.
4.
Gravity influences Qh because the veins are so compliant, and substantial quantities of blood tend to pool in the veins of dependent portions of the body. Respiration changes the pressure gradient between the intrathoracic and extrathoracic veins. Hence, respiration serves as an auxiliary pump, which may affect the mean level of Qh and induce rhythmic changes in stroke volume during the various phases of the respiratory cycle.
5.
In anticipation of exercise, vagus nerve impulses to the heart are inhibited and the sympathetic nervous system is activated by central command. The result is an increase in heart rate, myocardial contractile force, and regional vascular resistance. In addition, vascular resistance increases in the skin, kidneys, splanchnic regions, and inactive muscles and decreases markedly in the active muscles. The overall effect is a pronounced reduction in total peripheral resistance,
Eijsvogels TMH, Fernandez AB, Thompson PD. Are there deleterious cardiac effects of acute and chronic endurance exercise? Physiol Rev. 2016;96:99.